Institute for Nanoscience and Nanotechnology, Sharif University of Technology, P.O. Box 11365-11155, Tehran, Iran.
Department of Cell and Developmental Biology, School of Biological Sciences, College of Science, University of Tehran, Tehran, Iran.
Acta Biomater. 2021 Apr 1;124:191-204. doi: 10.1016/j.actbio.2021.01.029. Epub 2021 Jan 27.
Wound healing is a complex process based on the coordinated signaling molecules and dynamic interactions between the engineered scaffold and newly formed tissue. So far, most of the engineered scaffolds used for the healing of full-thickness skin wounds do not mimic the natural extracellular matrix (ECM) complexity and therefore are not able to provide an appropriate niche for endogenous tissue regeneration [1]. To address this gap and to accelerate the wound healing process, we present biomimetic bilayer scaffolds compositing of gelatin nanofibers (GFS) and photocrosslinkable composite hydrogels loaded with epidermal growth factors (EGF). The nanofibers operate as the dermis layer, and EGF-loaded composite hydrogels acted as the epidermis matrix for the full-thickness wound healing application. The hydrogels are composed of gelatin metacryloyl (GelMA) modified with silicate nanoplatelets (Laponite). To overcome the challenges of transdermal delivery of EGF, including short half-life and lack of efficient formulation precise, controlled delivery was attained by immobilization of EGF on Laponite. It is shown that the addition of 1wt% silicate nanoplatelet increases the compressive modulus of the hydrogels by 170%. In vitro wound closure analysis also demonstrated improved adhesion of the scaffolds to the native tissue by 3.5 folds. Moreover, the tunable hemostatic ability of the scaffolds due to the negatively charged nanoplatelets is shown. In an established excisional full-thickness wound model, an enhanced wound closure (up to 93.1 ± 1.5%) after 14 days relative to controls (GFS and saline-treated groups) is demonstrated. The engineered adhesive and hemostatic scaffolds with sustained release of the growth factors have the potential to stimulate complete skin regeneration for full-thickness wound healing.
伤口愈合是一个复杂的过程，基于工程支架与新形成的组织之间的协调信号分子和动态相互作用。到目前为止，大多数用于全层皮肤伤口愈合的工程支架都不能模拟天然细胞外基质（ECM）的复杂性，因此不能为内源性组织再生提供适当的小生境[1]。为了解决这一差距并加速伤口愈合过程，我们提出了仿生双层支架，由明胶纳米纤维（GFS）和光交联复合水凝胶组成，负载表皮生长因子（EGF）。纳米纤维作为真皮层，负载 EGF 的复合水凝胶作为全层伤口愈合应用的表皮基质。水凝胶由明胶甲基丙烯酰（GelMA）与硅酸盐纳米片（Laponite）改性而成。为了克服 EGF 经皮递送的挑战，包括半衰期短和缺乏有效的制剂，通过将 EGF 固定在 Laponite 上实现了精确的、受控的递送。结果表明，添加 1wt%硅酸盐纳米片可使水凝胶的压缩模量增加 170%。体外伤口闭合分析还表明，支架与天然组织的粘附性提高了 3.5 倍。此外，由于带负电荷的纳米片，支架具有可调的止血能力。在建立的切除全层伤口模型中，与对照组（GFS 和生理盐水处理组）相比，14 天后伤口闭合率提高了 93.1%±1.5%。具有生长因子持续释放功能的工程化粘合和止血支架具有刺激全层伤口愈合的完全皮肤再生的潜力。
